The IVGTT interpreted with the minimal model of glucose disappearance is a powerful tool to investigate glucose metabolism in vivo. The model provides two metabolic indices that measure glucose effectiveness, SG, and insulin sensitivity, SI, in a single individual. Since without a tracer it is extremely difficult to distinguish glucose disappearance rate, Rd, from hepatic glucose release, HGR, the indices SG and SI are composite parameters. To segregate the effect of glucose and insulin on Rd and HGR, a stable isotope-labeled IVGTT has been introduced, i.e. glucose tracer has been added to the glucose bolus. The stable isotope content of glucose was determined by mass spectrometry. The stable isotope-labeled glucose data interpreted with a new minimal model of glucose disappearance provides new indices of glucose effectiveness, SG, and insulin sensitivity, SI, that measure the effects of glucose and insulin, respectively, to enhance Rd only. The time course of HGR durin g the test can also be obtained by deconvolution. The relationships between SG, SI and SG, SI (designated cold and hot indices, respectively) have been subjected to theoretical analysis. It is now possible to explore further the relationships between the hot and cold indices, in particular by assessing the degree of correlation between SG and SI and between SG, and SI. Some unexpected relationships emerge between the cold and hot indices and we discuss them in the light of a number of methodological issues; single compartment assumption in the cold and hot minimal model, functional description of HGR embodied in the cold minimal model and validation studies of cold and hot indices.